The results of the CARTITUDE-1 clinical trial demonstrate outstanding and unprecedented long-term efficacy with ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory multiple myeloma.1 (See the July 2025 issue of The ASCO Post for a detailed discussion of the CARTITUDE-1 results.) With the right patient selection, ciltacabtagene autoleucel is an incredibly effective treatment option for patients with this blood cancer. Many patients in the study are able to lead a normal life off all myeloma treatments for many years. Given these striking results, I expect overall survival in myeloma to continue to improve.
Interpreting the Results of CARTITUDE-1
There are a few important points to consider when interpreting these results. First, do these results represent a cure? In one center where serial measurable residual disease (MRD) studies were done, all 12 patients who were progression-free for at least 5 years also achieved MRD negativity at 10–6 level and had no evidence of active disease on positron-emission tomography/computed tomography assessments. This opens the possibility that some patients in this cohort may be potentially cured, which is quite remarkable given that the trial participants had been heavily pretreated. However, we need more follow-up to determine whether there is a sustained plateau in the time to disease progression and/or the progression-free survival curve to establish curability and to determine the proportion of patients who can be cured.
S. Vincent Rajkumar, MD
Second, do these results in late-line settings mean that ciltacabtagene autoleucel can perform even better in earlier lines of treatment? To address this issue, we need to consider the benefits and the risks of such a move. There are real concerns about side effects with ciltacabtagene autoleucel, including late neurotoxicity. There are a lot of good treatments for earlier stages of relapsed myeloma with a long track record of efficacy and safety. In first relapse, the benefits and risks of ciltacabtagene autoleucel need to be compared with those of these established treatments on a case-by-case basis. The results of CARTITUDE-1 paradoxically support the idea that ciltacabtagene autoleucel may work just as well in later lines as in first relapse: the median progression-free survival in CARTITUDE-1 (median 6.5 prior lines of therapy) does not differ from the median progression-free survival seen in early-relapse settings.
Third, there are issues of access and cost. Myeloma treatments are characterized by high costs and disparities in accessibility. As current early-relapse treatments just start to become affordable, it is difficult to justify expensive replacements without more data on safety and efficacy in terms of appropriate sequencing.
Sequencing of Treatments in Myeloma
I look forward to additional results of studies with CAR T-cell therapy in earlier lines of treatment, including as a replacement for stem cell transplantation in front-line therapy. We do not have results from these trials yet. Outside of a clinical trial setting, I primarily recommend ciltacabtagene autoleucel for second- or later-relapse settings. However, it is reasonable to consider ciltacabtagene autoleucel for first relapse in younger patients with functional high-risk myeloma (defined as early relapse, typically within 12 months, after initial treatment).
CAR T-cell therapy competes in terms of sequencing with bispecific antibodies and in the future with new trispecific antibodies. These off-the-shelf antibody treatments have the advantage of being readily available for use, whereas we need at least a few weeks to institute CAR T-cell therapy.
Patient selection is critical in this therapy, since serious toxicity with ciltacabtagene autoleucel and other CAR T-cell products is higher if the disease is not well controlled. The outstanding results of CARTITUDE-1 cannot be achieved without appropriate patient selection and sufficient clinical expertise in managing the therapy and its side effects.
Overall, these results are very impressive and portend an exciting future for the field.
DISCLOSURE: Dr. Rajkumar reported no conflicts of interest.
REFERENCE
1. Voorhees PM, Martin TG, Lin Y, et al: Long-term (≥ 5 years) remission and survival after treatment with ciltacabtagene autoleucel in CARTITUDE-1 patients with relapsed/refractory multiple myeloma. 2025 ASCO Annual Meeting. Abstract 7507. Presented June 3, 2025.
Dr. Rajkumar is the Edward W. and Betty Knight Scripps Professor of Medicine at Mayo Clinic in Rochester, Minnesota.
